Pharmacokinetics and residues elimination of diclofenac sodium administration in pigs by a new HPLC/MS method

Yongjun Li; Haifeng Yang; Yaqin Wang; Shijin Bu

doi:10.14715/cmb/2019.65.1.6

Issue

Vol. 65 No. 1: Issue 1

Issue Published : February 4, 2019

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Pharmacokinetics and residues elimination of diclofenac sodium administration in pigs by a new HPLC/MS method

https://doi.org/10.14715/cmb/2019.65.1.6

Yongjun Li

The School of Animal Pharmaceuticals, Jiangsu Agri-animal Husbandry Vocational College, Taizhou 225300, China

Haifeng Yang

The School of Animal Pharmaceuticals, Jiangsu Agri-animal Husbandry Vocational College, Taizhou 225300, China

Yaqin Wang

Veterinary Medicine College / Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou Univercity, Yangzhou 225009, China

Shijin Bu

Veterinary Medicine College / Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou Univercity, Yangzhou 225009, China

Corresponding Author(s) : Shijin Bu

bu_shijin810@yeah.net

Cellular and Molecular Biology, Vol. 65 No. 1: Issue 1
Article Published : January 31, 2019

Abstract

Diclofenac sodium (DS) was the third generation non-steroidal drugs with analgesic and antipyretic properties. Owing to taking action faster, long lasting potency, good efficacy and low side effects, DS was widely used in the pharmaceutical industry. To further ensure animal food safety and consumer health, the rational usages regulations of DS and DS withdrawal time should be provided. In the present study, a new high performance liquid chromatography tandem mass spectrometry (HPLC/MS) method was first established for extracting and validating diclofenac sodium levels in edible porcine tissues. Meanwhile, the pharmacokinetics characteristics and residue elimination of intramuscular DS administration in pigs were also studied. We found DS eliminated quickly and the distribution was poor in vivo. After a single dose of 2.5 mg/kg body weight per day for continuous 3 days, the withdrawal time in the tissues of liver, kidney, sebum, muscle and administration site were 9.892 days, 5.116 days, 14.205 days, 5.444 days and 8.818 days, respectively. According to the double-sided 95% confidence interval, DS withdrawal period should be 15 days. These experiment evidences lay a good foundation on the rational usages regulations of DS and DS withdrawal time, which will be helpful for the animal food safety and consumer health.

Keywords

Diclofenac sodium Pharmacokinetics Pig Residue elimination HPLC/MS.

Li, Y., Yang, H., Wang, Y., & Bu, S. (2019). Pharmacokinetics and residues elimination of diclofenac sodium administration in pigs by a new HPLC/MS method. Cellular and Molecular Biology, 65(1), 36–40. https://doi.org/10.14715/cmb/2019.65.1.6

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References

Da Costa BR, Reichenbach S, Keller N, Nartey L, Wandel S, Jüni P, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. The Lancet. 2017; 390:e21-e33.
Menasse R, Hedwall PR, Kraetz J, Pericin C, Riesterer L, Sallmann A, et al. Pharmacological properties of diclofenac sodium and its metabolites. Scandinavian journal of rheumatology. Supplement. 1978; 5-16.
Ku EC, Lee W, Kothari HV, Scholer DW. Effect of diclofenac sodium on the arachidonic acid cascade. The American journal of medicine. 1986; 80:18-23.
Riendeau D, Percival MD, Boyce S, Brideau C, Charleson S, Cromlish W, et al. Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor. British journal of pharmacology. 1997; 121:105-117.
Kothari HV, Lee WH, Ku EC. An alternate mechanism for regulation of leukotriene production in leukocytes: studies with an anti-inflammatory drug, sodium diclofenac. Biochimica et biophysica acta. 1987; 921:502-511.
Altaher AY, Alkharfy KM, Al-Hadiya BM, Khan RM. Pharmacokinetics of diclofenac in sheep following intravenous and intramuscular administration. Veterinary anaesthesia and analgesia. 2006; 33:241-245.
Zorica P, Milena P, Milanka J. Pharmacokinetics of diclofenac in pigs after intramuscular administration of a single dose. Acta veterinaria. 2006; 56:323-331.
Taggart MA, Senacha KR, Green RE, Jhala YV, Raghavan B, Rahmani AR, et al. Diclofenac residues in carcasses of domestic ungulates available to vultures in India. Environment international. 2007; 33:759-765.
Sacher F, Lange FT, Brauch HJ, Blankenhorn I. Pharmaceuticals in groundwaters: analytical methods and results of a monitoring program in Baden-Württemberg, Germany. Journal of chromatography A. 2001; 938:199-210.
Kümmerer K. Pharmaceuticals in the environment: sources, fate, effects and risks. Springer Science & Business Media. 2008.
Triebskorn R, Casper H, Heyd A, Eikemper R, Köhler HR, Schwaiger J. Toxic effects of the non-steroidal anti-inflammatory drug diclofenac: Part II. Cytological effects in liver, kidney, gills and intestine of rainbow trout (Oncorhynchus mykiss). Aquatic toxicology. 2004; 68:151-166.
Dietrich D, Prietz A. Fish embryotoxicity and teratogenicity of pharmaceuticals, detergents and pesticides regularly detected in sewage treatment plant effluents and surface waters. Toxicologist. 1999; 48:151.
Wang Z, Li X, Su D, Li Y, Wu L, Wang Y, et al. Residue depletion of imidocarb in Swine tissue. Journal of agricultural and food chemistry. 2009; 57:2324-2328.
Munjal S, Gautam A, Okumu F, McDowell J, Allenby K. Safety and pharmacokinetics of single and multiple intravenous bolus doses of diclofenac sodium compared with oral diclofenac potassium 50 mg: A randomized, parallel-group, single-center study in healthy subjects. Journal of clinical pharmacology. 2016; 56:87-95.
Delmas JM, Chapel AM, Gaudin V, Sanders P. Pharmacokinetics of flumequine in sheep after intravenous and intramuscular administration: bioavailability and tissue residue studies. Journal of veterinary pharmacology and therapeutics. 1997; 20:249-257.

References

Da Costa BR, Reichenbach S, Keller N, Nartey L, Wandel S, Jüni P, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. The Lancet. 2017; 390:e21-e33.

Menasse R, Hedwall PR, Kraetz J, Pericin C, Riesterer L, Sallmann A, et al. Pharmacological properties of diclofenac sodium and its metabolites. Scandinavian journal of rheumatology. Supplement. 1978; 5-16.

Ku EC, Lee W, Kothari HV, Scholer DW. Effect of diclofenac sodium on the arachidonic acid cascade. The American journal of medicine. 1986; 80:18-23.

Riendeau D, Percival MD, Boyce S, Brideau C, Charleson S, Cromlish W, et al. Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor. British journal of pharmacology. 1997; 121:105-117.

Kothari HV, Lee WH, Ku EC. An alternate mechanism for regulation of leukotriene production in leukocytes: studies with an anti-inflammatory drug, sodium diclofenac. Biochimica et biophysica acta. 1987; 921:502-511.

Altaher AY, Alkharfy KM, Al-Hadiya BM, Khan RM. Pharmacokinetics of diclofenac in sheep following intravenous and intramuscular administration. Veterinary anaesthesia and analgesia. 2006; 33:241-245.

Zorica P, Milena P, Milanka J. Pharmacokinetics of diclofenac in pigs after intramuscular administration of a single dose. Acta veterinaria. 2006; 56:323-331.

Taggart MA, Senacha KR, Green RE, Jhala YV, Raghavan B, Rahmani AR, et al. Diclofenac residues in carcasses of domestic ungulates available to vultures in India. Environment international. 2007; 33:759-765.

Sacher F, Lange FT, Brauch HJ, Blankenhorn I. Pharmaceuticals in groundwaters: analytical methods and results of a monitoring program in Baden-Württemberg, Germany. Journal of chromatography A. 2001; 938:199-210.

Kümmerer K. Pharmaceuticals in the environment: sources, fate, effects and risks. Springer Science & Business Media. 2008.

Triebskorn R, Casper H, Heyd A, Eikemper R, Köhler HR, Schwaiger J. Toxic effects of the non-steroidal anti-inflammatory drug diclofenac: Part II. Cytological effects in liver, kidney, gills and intestine of rainbow trout (Oncorhynchus mykiss). Aquatic toxicology. 2004; 68:151-166.

Dietrich D, Prietz A. Fish embryotoxicity and teratogenicity of pharmaceuticals, detergents and pesticides regularly detected in sewage treatment plant effluents and surface waters. Toxicologist. 1999; 48:151.

Wang Z, Li X, Su D, Li Y, Wu L, Wang Y, et al. Residue depletion of imidocarb in Swine tissue. Journal of agricultural and food chemistry. 2009; 57:2324-2328.

Munjal S, Gautam A, Okumu F, McDowell J, Allenby K. Safety and pharmacokinetics of single and multiple intravenous bolus doses of diclofenac sodium compared with oral diclofenac potassium 50 mg: A randomized, parallel-group, single-center study in healthy subjects. Journal of clinical pharmacology. 2016; 56:87-95.

Delmas JM, Chapel AM, Gaudin V, Sanders P. Pharmacokinetics of flumequine in sheep after intravenous and intramuscular administration: bioavailability and tissue residue studies. Journal of veterinary pharmacology and therapeutics. 1997; 20:249-257.

Author Biography

Shijin Bu, Veterinary Medicine College / Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou Univercity, Yangzhou 225009, China

Department of Veterinary Pharmacology and Toxicology